Infertility affects 1 in 6 couples of reproductive age globally (Harris, 2023). In 40 % of couples with infertility, male factor infertility is the primary cause (Skakkebaek et al., 2016), with a rising trend (Liang et al., 2025). The most effective infertility treatment is assisted reproductive technology (ART) (Kissin et al., 2015). Although the annual number of ART cycles in China has exceeded 1 million, the rate of live births remains only 0.3 million (Kong et al., 2023). In addition to ART technology itself, a growing number of epidemiological studies have shown that environmental endocrine-disrupting chemicals (EDCs) play a role in inversely affecting embryo growth and development, and further are associated with adverse pregnancy outcomes (Hauser et al., 2016; Mínguez-Alarcón et al., 2019; Deng et al., 2023).

Bisphenol A (BPA) is ubiquitous in populations, as it is a raw material used in various consumer products such as reusable containers of food and beverages (Rochester, 2013; Michałowicz, 2014). Biomonitoring studies have reported that >90 % of the general population have detectable urinary BPA concentrations (Calafat et al., 2008). Due to its multiple toxicological hazards and potential adverse health effects (Ma et al., 2019), the utilization of BPA has prompted the implementation of regulatory measures in numerous countries, resulting in the emergence of alternative substances such as bisphenol F (BPF) being labeled as BPA-free products increasingly used in the market (Rochester and Bolden, 2015). However, measured levels of BPF in human beings have shown increasing exposure trends in recent years (Ye et al., 2015; Jiang et al., 2023).

The associations of maternal exposure to bisphenols with reproductive and developmental endpoints are a frequent focus in epidemiological studies. Our prior studies found inverse associations between bisphenols and ovarian reserve as evidenced by altered reproductive hormone levels and decreased antral follicle count among women undergoing ART treatment (Zhang et al., 2023, 2024). In addition, maternal exposure to bisphenols on in vitro fertilization (IVF) outcomes has been well-studied (Ehrlich et al., 2012; Mínguez-Alarcón et al., 2019; Radwan et al., 2020). However, paternal exposure before conception is often overlooked (Oldereid et al., 2018). Paternal-mediated toxicity of reproductive and developmental effects has long been proposed (Rando, 2012; Braun et al., 2017). Paternal exposure might affect offspring health, mediated by sperm epigenome (Chapin et al., 2004; Chen et al., 2016; Siddeek et al., 2018), and the dysregulation of the epigenetic process leads to impaired embryonic development, fertilization, and pregnancy (Robinson et al., 2012; Kumar et al., 2013). Previous epidemiological studies have reported significant inverse associations between IVF outcomes and paternal exposure to phthalate metabolites (Dodge et al., 2015a, Dodge et al., 2015b; Mínguez-Alarcón et al., 2021) and organophosphate flame retardant metabolites (Carignan et al., 2018), but non-significant associations have also been reported in paternal exposure to BPA (Dodge et al., 2015a, Dodge et al., 2015b). Whether BPA has similar adverse effects to the above-mentioned EDCs in IVF outcomes remains largely unknown. Furthermore, to our knowledge, no human studies have evaluated the associations of paternal concentrations to BPF on IVF outcomes.

Therefore, to address this research gap, we aimed to explore the relationships between paternal exposure to BPA and BPF and IVF outcomes among men from a couple-based prospective IVF cohort in Shenyang, China.